Biomarkers for Agrochemicals and Toxic Substances. Applications and Risk Assessment

282 Pages·1996·27.67 MB·English

by  Jerry N. Blancato

Biomarkers for Agrochemicals
and Toxic Substances
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
ACS SYMPOSIUM SERIES 643
Biomarkers for Agrochemicals
and Toxic Substances
Applications and Risk Assessment
Jerry N. Blancato, EDITOR
U.S. Environmental Protection Agency
Robert N. Brown, EDITOR
U.S. Environmental Protection Agency
Curtis C. Dary, EDITOR
U.S. Environmental Protection Agency
Mahmoud Abbas Saleh, EDITOR
Texas Southern University
Developed from a symposium sponsored
by the Division of Agrochemicals
American Chemical Society, Washington, DC
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
Library of Congress Cataloging in Publication Data
Biomarkers for agrochemicals and toxic substance: applications and risk
assessment / Jerry N. Blancato... [et al.], editor.
p. cm.—(ACS symposium series, ISSN 0097-6156; 643)
"Developed from a symposium sponsored by the Division of
Agrochemicals at the 209th National Meeting of the American Chemical
Society, Anaheim, California, April 2-7, 1995."
Includes bibliographical references and indexes.
ISBN 0-8412-3449-3
1. Agricultural chemicals—Health aspects—Congresses.
2. Biochemical markers—Congresses. 3. Endocrine toxicology-
Congresses. 4. Agricultural chemicals—Environmental aspects-
Congresses.
I. Blancato, Jerry Ν. II. American Chemical Society. Division of
Agrochemicals. III. American Chemical Society. Meeting (209th: 1995:
Anaheim, Calif.). IV. Series.
[DNLM: 1. Agrochemicals—congresses. 2. Hazardous
Substances—congressses. 3. Biological Markers—congresses.
4. Environmental Exposure—prevention & control—United States-
congresses. WA 465 B620 1996]
RA1270.A4B55 1996
615.9—dc20
DNLM/DLC
for Library of Congress 96-28772
CIP
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In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
Advisory Board
ACS Symposium Series
Robert J. Alaimo Cynthia A. Maryanoff
Procter & Gamble Pharmaceuticals R. W. Johnson Pharmaceutical
Research Institute
Mark Arnold
University of Iowa Roger A. Minear
University of Illinois
David Baker at Urbana-Champaign
University of Tennessee
Omkaram Nalamasu
Arindam Bose AT&T Bell Laboratories
Pfizer Central Research
Vincent Pecoraro
Robert F. Brady, Jr. University of Michigan
Naval Research Laboratory
George W. Roberts
Mary E. Castellion North Carolina State University
ChemEdit Company
John R. Shapley
Margaret A. Cavanaugh University of Illinois
National Science Foundation at Urbana-Champaign
Arthur B. Ellis Douglas A. Smith
University of Wisconsin at Madison Concurrent Technologies Corporation
Gunda I. Georg L. Somasundaram
University of Kansas DuPont
Madeleine M. Joullie Michael D. Taylor
University of Pennsylvania Parke-Davis Pharmaceutical Research
Lawrence P. Klemann William C. Walker
Nabisco Foods Group DuPont
Douglas R. Lloyd Peter Willett
The University of Texas at Austin University of Sheffield (England)
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
Foreword
THE ACS SYMPOSIUM SERIES was first published in 1974 to
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ers) of the symposium, who become the editor(s) of the book.
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In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
Preface
THE RISK ASSESSMENT PROCESS has received increased attention over
the past few years. The National Research Council, the U.S. Congress,
and numerous international bodies have all discussed its importance.
There are considerable uncertainties with the probabilistic estimates of
risk. Risk assessments consist of many components involving several
scientific disciplines. Exposure assessment is often the weak link in risk
assessments. While a treatise on exposure assessment is outside the
scope of this volume, measurements of concentrations in environmental
media and in biological fluids and tissues are important cornerstones.
These measurements are often expensive and time-consuming. We need
accurate, quick, and cost-effective measurement techniques. In addition,
we need interpretive methods to assess exposure and risk to xenobiotics.
Public concerns about agrochemicals and toxic substances are great.
The media frequently report on these areas, alerting people to newly per
ceived dangers, both real and imagined. The public finds pesticides in
food products and in drinking water especially disconcerting. For exam
ple, we have grown more aware of the role of agrochemicals as possible
endocrine disruptors.
Biomarkers and biomonitoring, the subjects of this volume, offer
exciting opportunities to understand more completely environmental,
chemical, and physiologic processes by providing useful measures of
chemicals and their breakdown products. Many chapters in this volume
show and discuss such new methods and their field applications. How
ever, to take full advantage of any new measurement or monitoring stra
tegies, we should understand all the mechanistic processes. Full under
standing is not always possible; progress is made in stages.
This volume was developed from the work presented at the 209th
National Meeting of the American Chemical Society, titled "Biomarkers
for Agrochemicals and Toxic Substances," sponsored by the Division of
Agrochemicals, in Anaheim, California, April 2-7, 1995. It focuses not
only on measurement techniques and applications but also on new and
innovative thinking regarding the interpretation of measurement results.
Several chapters deal with the application of results to the exposure and
risk assessment process. Other chapters discuss new physiologic end
points as markers of exposure and effect. This integrated picture is more
fully discussed in the first chapter.
xi
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
We wish to acknowledge the efforts of all contributing authors in pro
viding informative and insightful chapters. We also acknowledge the
assistance and patience of our acquisitions editor, Michelle Althuis.
JERRY N. BLANCATO
ROBERT N. BROWN
CURTIS C. DARY
Characterization Research Division
National Exposure Research Laboratory
U.S. Environmental Protection Agency
944 East Harmon Avenue
Las Vegas, NV 89193-3478
MAHMOUD ABBAS SALEH
Environmental Chemistry and Toxicology Laboratory
Department of Chemistry
3100 Cleburne Avenue
Texas Southern University
Houston, TX 77004
May 30, 1996
xii
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
Chapter 1
Relationship of Biomarkers of Exposure
to Risk Assessment and Risk Management
Curtis C. Dary, James J. Quackenboss,
Charles H. Nauman, and Stephen C. Hern
Characterization Research Division, National Exposure Research
Laboratory, U.S. Environmental Protection Agency, 944 East Harmon,
Las Vegas, NV 89193-3478
An "environmental health paradigm" has been proposed for setting
priorities in risk assessment for pesticides. This paradigm serves as a
useful template for depicting the chain of events that relate sources of
exposure with adverse environmental and human health outcomes. The
paradigm is based on multiroute and multipathway exposure from contact
with contaminants in multimedia as modulated by the magnitude,
frequency, and duration of exposure. As part of this risk assessment
paradigm, biomarkers integrate routes, media, and pathways of exposure
so that scientifically defensible risk characterizations can be realized.
Biomarkers of exposure are indicators of current or historical contact with
an environmental agent. Moreover, biomarkers serve to evaluate the
completeness of exposure assessment information by associating
environmental or source information, exposure measurements, and
epidemiological and human activity data with internal dose. Biomarkers
may take the form of the unchanged agent itself or its metabolites, an
adduct or biochemical indicator depending on the source and route of
exposure, and the metabolism, storage, and excretion and physicochemical
properties of the agent. This paper will review the use of biomarkers of
exposure and explore the relationship biomarkers assume within the risk
assessment or "environmental health" paradigm.
Risk is a function of exposure and hazard and risk assessment is the process used to
evaluate the probability of exposure and the magnitude and character of the hazard
posed to human health and ecosystems by environmental stressors such as pollution
and alterations in the quality of habitats (1,2). The risk assessment process consists
of hazard identification, dose-response assessment, exposure assessment and risk
characterization. Hazard identification involves the experimental study of toxicity
in test organisms and the examination and evaluation of reports of exposure
incidents and epidemiological research. The potency of a stressor is determined
experimentally through a dose-response assessment. An exposure assessment
This chapter not subject to U.S. copyright
Published 1996 American Chemical Society
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
1. DARY ETAL Biomarkers and Risk Assessment 3
determines the nature and size of the population or ecosystem at risk together with
the frequency, duration and magnitude of the exposure to the stressor. The data
collected through the first three elements, hazard identification, dose-response
assessment and exposure assessment, are used in risk characterization to qualitatively
or quantitatively estimate or predict the likelihood of an adverse health outcome.
Components of the Paradigm
Exposure assessment has been generally considered to be the weak link in hazard
evaluation and the assessment of risk to toxic substances including pesticides (3). As
depicted by Pirkle et al. (4) and recast to explore the pesticide exposure situation
(Exhibit 1), exposure assessment represents the preponderance of elements along the
spine of the environmental health paradigm that guides research in risk assessment
and risk management decisions (5). The environmental health paradigm for the
pesticide situation looks to a clear relationship between media concentrations, the
rate of exposure and adverse environmental health outcomes. Monitoring exposure
through the use of biomarkers provides a measure of the amount of the agent
transferred into an organism independent of the source or medium.
Sources. For the pesticide situation, the source of the exposure is generally
controlled through regulation as specified under the Federal Insecticide Fungicide
and Rodenticide Act (FIFRA. 7 U.S.C. 136 a-c, 136v.). The active ingredients and
formulations of pesticide products have been rationally designed and packaged for
the actuation of product at prescribed rates to control target pests in accordance with
the lawful labeling instructions. The product label contains approved conditions for
use, special restrictions, hazard warnings and general information about the product
(6). Conformance with the labeling instructions would be expected to reduce
exposure to the user and other non target organisms while delivering the product to
the intended target. Exposure would be expected to occur to the user through the
occupational activities required during handling while exposure to nontarget
organisms might occur through the incidental contact with residues. Thus the source
of exposure along the environmental health paradigm for pesticides (Exhibit 1) is set
along parallel tracts for occupational and incidental exposure.
Environmental Concentrations. Occupational exposure is clearly a human
condition where the user is expected to come into contact with relatively high
environmental concentrations of the product in different exposure media during
mixing, loading, application, and harvesting (7,8). As depicted in Exhibit 1, the
sources of occupational exposure would be expected to be the formulation
concentrate, the end use product, the application rate and the commodity or target.
The formulation concentrate might refer to emulsifiable concentrates, wettable
powders and certain dry flowables and microencapulated formulations that are mixed
with water to produce the end use product (9). The end use product may also be
"ready to use" as an aerosol to be actuated at specified application rates. The
In Biomarkers for Agrochemicals and Toxic Substances; Blancato, J., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1996.